2ouc
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Crystal structure of the MAP kinase binding domain of MKP5
OverviewOverview
MAP kinase phosphatases (MKPs) have crucial roles in regulating the, signaling activity of MAP kinases and are potential targets for drug, discovery against human diseases. These enzymes contain a catalytic domain, (CD) as well as a binding domain (BD) that help recognize the target MAP, kinase. We report here the crystal structures at up to 2.2 A resolution of, the BD and CD of human MKP5 and compare them to the known structures from, other MKPs. Dramatic structural differences are observed between the BD of, MKP5 and that of MKP3 determined previously by NMR. In particular, the, cluster of positively charged residues that is important for MAP kinase, binding is located in completely different positions in the two, structures, with a distance of 25 A between them. Moreover, this cluster, is alpha-helical in MKP5, while it forms a loop followed by a beta-strand, in MKP3. These large structural differences could be associated with the, distinct substrate preferences of these phosphatases, but further studies, are needed to confirm this. The CD of MKP5 is observed in an active, conformation, and two loops in the active site have backbone shifts of up, to 5 A relative to the inactive CDs from other MKPs.
About this StructureAbout this Structure
2OUC is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of the MAP kinase binding domain and the catalytic domain of human MKP5., Tao X, Tong L, Protein Sci. 2007 May;16(5):880-6. Epub 2007 Mar 30. PMID:17400920
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